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为Notch搭建舞台:果蝇的Su(H)-无毛发抑制复合物

Setting the Stage for Notch: The Drosophila Su(H)-Hairless Repressor Complex.

作者信息

Borggrefe Tilman, Oswald Franz

机构信息

Institute of Biochemistry, University of Giessen, Giessen, Germany.

Center for Internal Medicine, Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany.

出版信息

PLoS Biol. 2016 Jul 26;14(7):e1002524. doi: 10.1371/journal.pbio.1002524. eCollection 2016 Jul.

DOI:10.1371/journal.pbio.1002524
PMID:27458807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4961364/
Abstract

Notch signaling is iteratively used throughout development to maintain stem cell potential or in other instances allow differentiation. The central transcription factor in Notch signaling is CBF-1/RBP-J, Su(H), Lag-1 (CSL)-Su(H) in Drosophila-which functions as a molecular switch between transcriptional activation and repression. Su(H) represses transcription by forming a complex with the corepressor Hairless (H). The Su(H)-repressor complex not only competes with the Notch intracellular domain (NICD) but also configures the local chromatin landscape. In this issue, Yuan and colleagues determined the structure of the Su(H)/H complex, showing that a major conformational change within Su(H) explains why the binding of NICD and H is mutually exclusive.

摘要

Notch信号通路在整个发育过程中反复被用于维持干细胞潜能,或在其他情况下促进分化。Notch信号通路中的核心转录因子是CBF-1/RBP-J、果蝇中的Su(H)、Lag-1(CSL)-Su(H),它作为转录激活和抑制之间的分子开关发挥作用。Su(H)通过与共抑制因子Hairless(H)形成复合物来抑制转录。Su(H)-共抑制因子复合物不仅与Notch细胞内结构域(NICD)竞争,还会塑造局部染色质景观。在本期杂志中,Yuan及其同事确定了Su(H)/H复合物的结构,表明Su(H)内的一个主要构象变化解释了为什么NICD和H的结合是相互排斥的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0908/4961364/53edb35683e1/pbio.1002524.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0908/4961364/e6a9c995b35a/pbio.1002524.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0908/4961364/53edb35683e1/pbio.1002524.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0908/4961364/e6a9c995b35a/pbio.1002524.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0908/4961364/53edb35683e1/pbio.1002524.g002.jpg

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PLoS Biol. 2016 Jul 12;14(7):e1002509. doi: 10.1371/journal.pbio.1002509. eCollection 2016 Jul.
2
A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes.一种涉及NCoR和KMT2D的磷酸化依赖性机制控制着Notch靶基因处的允许染色质状态。
Nucleic Acids Res. 2016 Jun 2;44(10):4703-20. doi: 10.1093/nar/gkw105. Epub 2016 Feb 23.
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The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFβ/BMP and hypoxia pathways.
Nat Commun. 2023 Jan 27;14(1):439. doi: 10.1038/s41467-023-36179-8.
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Genetic and Molecular Interactions between , a Novel Allele of the Notch Antagonist Hairless, and the Histone Chaperone Asf1 in .Notch 拮抗剂 Hairless 的新型等位基因 和组蛋白伴侣 Asf1 之间的遗传和分子相互作用。
Genes (Basel). 2023 Jan 13;14(1):205. doi: 10.3390/genes14010205.
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α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain.α-苯丙氨酰 tRNA 合成酶通过其 N 端结构域与 Notch 信号通路竞争。
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